The effect of lesions of the cerebral cortex and of the hippocampus on the neurochemical characteristics and distribution of the catecholaminergic neurons innervating, the regions will be studied. Lesions of the hippocampus will be made by stereotaxic injection of kainic acid, a conformationally restricted analogue of glutamate; this agent causes a selective degeneration of neurons with cell bodies in the injected region but spares axons of passage and of termination as shown by studies performed under this research grant. The effects of the lesion on the catecholaminergic terminals in the injected hippocampus and in ipsilateral and contralateral cortex will be monitored with regard to catecholamine levels and the activity of the biosynthetic enzymes for catecholamines. The acute and chronic effects of the lesion on noradrenergic fiber distribution will be monitored by immunohistochemical techniques utilizing a homospecific antibody to rat dopamine-hydroxylase. Destruction of neurons intrinsic to the cerebral cortex will be made at early stages of cortical development by treatment with an alkylating agent. The effects of the differential loss of cortical neurons on the catecholaminergic innervation will be assessed by neurochemical assays and immunohistochemical techniques.